Local resection via partial lamellar sclerouvectomy for ciliary body tumors - a case series.

BACKGROUND: Ciliary body tumor is extremely rare and treatment is challenging. The aim of this study is to present our experience in treating this rare entity, especially large tumors with more than 5 clock hours of involvement, and to evaluate the surgical outcomes and complications of local resection via partial lamellar sclerouvectomy in four cases of ciliary body tumors in China. METHODS: Four patients with ciliary body tumors underwent partial lamellar sclerouvectomy between October 2019 and April 2023 in Shanghai General Hospital, China. Tumor features, histopathologic findings, complications, visual acuity, and surgical outcomes were reviewed at a mean follow-up of 20.8 months. RESULTS: Four patients with a mean age of 31.8 years were included in this study. The histopathological diagnosis was adenoma of non-pigmented ciliary epithelium (ANPCE), schwannoma, and multiple ciliary body pigment epithelial cysts. The mean largest tumor base diameter was 6.00 mm (range: 2.00-10.00) and the mean tumor thickness was 3.50 mm (range: 2.00-5.00). Preoperative complications included cataract in 3 (75%) eyes, lens dislocation in 2 (50%), and secondary glaucoma in 1 (25%). Temporary ocular hypotonia was observed in one case and no other postoperative complications were observed. At a mean follow-up of 20.8 months, the best corrected visual acuity increased in 3 eyes and was stable in 1 eye. Tumor recurrence was absent in all eyes. All patients were alive at the end of follow-up. CONCLUSIONS: Local tumor resection via PLSU is useful in the treatment of ciliary body tumors, including large tumors occupying more than five clock hours of pars plicata. Surgery-related complications were manageable with adequate preoperative assessment and careful operation during surgery.

Impact of tumour volume and treatment delay on the outcome after linear accelerator-based fractionated stereotactic radiosurgery of uveal melanoma.

BACKGROUND/AIMS: Primary radiation therapy is used to treat malignant uveal melanoma (UM). We report our single-centre experience with fractionated radiosurgery (fSRS) with a linear accelerator (LINAC) after specific adaptation for small target volumes with HybridArc. METHODS: From October 2014 to January 2020, 101 patients referred to Dessau City Hospital with unilateral UM underwent fSRS with 50 Gy given in five fractions on five consecutive days. Primary endpoints were local tumour control, globe preservation, metastasis and death. Potential prognostic features were analysed. Kaplan-Meier analysis, Cox proportional hazards model and linear models were used for calculations. RESULTS: The median baseline tumour diameter was 10.0 mm (range, 3.0-20.0 mm), median tumour thickness 5.0 mm (range, 0.9-15.5 mm) and median gross tumour volume (GTV) 0.4 cm³ (range, 0.2-2.6 cm³). After a median follow-up of 32.0 months (range, 2.5-76.0 months), 7 patients (6.9%) underwent enucleation: 4 (4.0%) due to local recurrence and 3 (3.0%) due to radiation toxicities, and 6 patients (5.9%) revealed tumour persistence with a GTV exceeding 1.0 cm³. Of 20 patients (19.8%) who died, 8 (7.9%) were tumour-related deaths. Twelve patients (11.9%) suffered from distant metastasis. GTV showed an impact on all endpoints, and treatment delay was associated with reduced odds of eye preservation. CONCLUSION: LINAC-based fSRS with static conformal beams combined with dynamic conformal arcs and discrete intensity-modulated radiotherapy results in a high tumour control rate. The tumour volume is the most robust physical prognostic marker for local control and disease progression. Avoiding treatment delay improves outcomes.

Multifocal choroidal melanoma: a clinicohistopathological correlation.

A woman in her late 50s presented with on-and-off redness and diminution of vision in her left eye for 6 months. Her best corrected visual acuity was 20/40 in the right eye and hand motion in the left eye. Anterior segment examination revealed a greyish-white lesion extending from 3 to 6 o'clock hours posterior to the iris and protruding into the anterior chamber. Left eye B-scan ultrasonography showed a multifocal choroidal lesion, a smaller one involving the posterior pole, and a larger lesion involving the complete nasal quadrant and anteriorly extending to the ciliary body and iris. Fine-needle aspiration biopsy performed from the anterior lesion showed a possible neoplastic aetiology of melanocytic origin of the cells. Finally, the patient underwent left eye enucleation with a ball implant. Histopathological examination of the enucleated eye confirmed the final diagnosis of multifocal choroidal melanoma involving the adjacent ciliary body and iris.

An empirical approach to the definition of the target margins in eye radiosurgery.

INTRODUCTION: A system for stabilizing and monitoring eye movements during LINAC-based photon beam one single fraction stereotactic radiotherapy was developed at our Institution. This study aimed to describe the feasibility and the efficacy of our noninvasive optical localization system that was developed, tested, and applied in 20 patients treated for uveal melanoma. METHODS: Our system consisted of a customized thermoplastic mask to immobilize the head, a gaze fixation LED, and a digital micro-camera. The localization procedure, which required the active collaboration of the patient, served to monitor the eye movements during all phases of the treatment, starting from the planning computed tomography up to the administration of radiotherapy, and allowed the operators to suspend the procedure and to interact with the patient in case of large movements of the pupil. RESULTS: Twenty patients were treated with stereotactic radiosurgery (27 Gy in one fraction) for primary uveal melanoma. All patients showed a good tolerance to the treatment; until now, all patients were in local control during the follow up and one died for distant progression 6 months after radiosurgery. CONCLUSIONS: This study showed that this noninvasive technique, based on eye position control, is appropriate and can contribute to the success of LINAC-based stereotactic radiotherapy. A millimetric safety margin to the clinical target volume was adequate to take account for the organ movement. All patients treated till now showed a good local control; failures in the disease control were due to metastatic spread.

Stereotactic radiosurgery for medium and large uveal melanoma with a non-invasive eye immobilization device, a single institutional case series.

PURPOSE: To investigate the treatment outcome, visual outcome, and adverse effects of five-fraction stereotactic radiosurgery (SRS) to medium- and large-sized uveal melanoma with a non-invasive eye immobilization device. METHODS: Medical records of 14 patients with uveal melanoma receiving SRS with a total dose of 50 Gy in five fractions from 2008 to 2017 were retrospectively reviewed. A non-invasive eye fixation device was used to achieve and monitor eye immobilization. RESULTS: Local tumor control rates were 85.7% and 75.0% at 2 and 5 years, respectively. The average tumor diameter decreased significantly from 10.0 ± 3.21 mm to 8.36 ± 3.71 mm (p = 0.038) 15 months after SRS, while the average tumor thickness decreased significantly from 5.45 ± 2.21 mm to 4.34 ± 2.29 (p = 0.036) 21 months after SRS. The 5-year metastasis-free survival was 87.5%. The mean best-corrected visual acuity (BCVA) deteriorated from logMAR 0.296 at baseline to logMAR 1.112 at the last individual follow-up visits (p < 0.001). Adverse effects of SRS were comparable to those reported with proton-beam radiotherapy or Gamma knife therapy. CONCLUSION: SRS combined with a non-invasive eye immobilization device is an effective and safe alternative eye-preserving treatment for medium- to large-sized uveal melanoma. BCVA at 3 months may be a predictor for BCVA at 1 year.

Gamma Knife Radiosurgery for Uveal Melanoma: Our Experience and Thematic Review.

Background: Various therapies ranging from plaque brachytherapy to enucleation have been applied in uveal melanomas (UM). A gamma knife (GK) is the gold standard modality for head and neck radiation therapy with enhanced precision owing to the paucity of moving parts. The literature on GK usage in UM is rich with the methodology and nuances of GK applications undergoing constant change. Objectives: This article reports on the authors' experience in using GK for tackling UM followed by a thematic review of the evolution of GK therapy for UM. Materials and Methods: Clinical and radiological data of patients with UM treated with GK at the All India Institute of Medical Sciences, New Delhi, from March 2019 to August 2020 was analyzed. A systematic search for comparative studies and case series evaluating GK usage in UM was performed. Results: Seven UM patients underwent GK, with the median dose being 28 Gy at 50%. All patients underwent clinical follow-up and 3 patients had a radiological follow-up. Six (85.7%) eyes were preserved at follow-up, and 1 (14.28%) patient developed radiation-induced cataract. There was a reduction in tumor volume in all patients with radiological follow-up with the minimum being a 33.06% reduction in size compared to the presenting volume and the maximum being the complete disappearance of tumor at follow-up. A total of 36 articles presenting various facets of GK usage in UM have been thematically reviewed. Conclusion: GK can be a viable and effective eye-preserving option for UM with catastrophic side effects becoming rare owing to progressive reduction in radiation dose.

Factors affecting eye conservation and metastasis in posterior uveal melanomas.

PURPOSE: To determine the effect of patient and tumor features and different treatments on eye removal (enucleation or exenteration) and metastasis in posterior uveal melanoma (PUM). METHODS: Retrospective analysis. Patient age (≤60 vs >60 years), sex (female vs male), visual acuity (VA, ≤20/40 vs >20/40), largest tumor basal diameter (LTBD), tumor thickness, tumor stage according to American Joint Committee on Cancer (AJCC) 8th edition, ciliary body involvement, distance to optic disc (OD)/fovea (≤3 mm vs >3 mm), OD involvement, and histopathology were evaluated. Primary treatment options were transpupillary thermotherapy, plaque radiotherapy, Cyberknife radiosurgery, exoresection, and eye removal. Risk factors for primary eye removal were determined using logistic regression test and those for secondary eye removal and metastasis with Cox regression analysis. RESULTS: Of 387 cases, 153 (39.5%) underwent primary eye removal. Multivariable risk factors for primary eye removal included AJCC tumor stage (p = 0.001, OR:4.586; p < 0.001, OR:34.545; p < 0.001, OR:103.468 for stages T2, T3, and T4 vs stage T1, respectively), and VA≤20/40 (p = 0.014, OR:2.597). Multivariable risk factors for secondary eye removal were VA≤20/40 (p = 0.019, RR:2.817) and AJCC stage T3 vs T1 (p = 0.021, RR:2.666). Eye preservation rates in patients undergoing eye-conserving treatments were 80.3%, 69.6%, and 51.5% at 5, 10, and 15 years, respectively. Metastasis-free survival rates were 81.0%, 73.0%, and 56.7% at 5, 10, and 15 years, respectively. Multivariable risk factors for metastasis included eye removal as primary treatment (p = 0.005, RR:2.828) and mixed type histopathology (p < 0.001, RR:4.804). DISCUSSION: Early diagnosis is crucial for both eye preservation and survival in PUM. Increasing AJCC tumor stage and lower VA were risk factors for eye removal in this study. Mixed type histopathology and primary eye removal were risk factors for metastasis.

A Novel Method for Transillumination.

PURPOSE: To introduce a cost-efficient device for transillumination in the management of uveal melanoma. METHODS: Todorich Illuminated Depressor is a ball-point depressor, designed to work with the 23-, 25- and 27-gauge Alcon Constellation endoillumination. It was invented to allow indentation and peripheral vitreous visualization for vitrectomy. RESULTS: Todorich depressor combined with endoillumination can also work as a device for transillumination for tumor localization. We started using this method of transillumination for the management of uveal melanomas since September 2020 and have successfully performed Ru-106 plaque brachytherapy for 10 cases of uveal melanoma. Three were large choroidal melanoma cases, and en bloc tumor resection by partial lamellar sclerouvectomy was successfully performed after precise localization of tumors using this method. CONCLUSION: Alcon Constellation endoillumination capped with Todorich Illuminated Depressor is an affordable and viable alternative for transillumination of intraocular tumors.

Post-enucleation outcomes of patients with uveal melanoma in Scotland.

BACKGROUND/OBJECTIVES: To investigate post-enucleation outcomes and assess the effect of extrascleral extension (ESE) on these outcomes for patients with uveal melanoma (UM) managed at a tertiary referral centre in Scotland. SUBJECTS/METHODS: Retrospective review of all cases of UM managed by the Scottish Ocular Oncology Service for which enucleation was undertaken between 13/03/2008 and 31/12/2020. Primary outcomes were length of survival, time-to-metastasis (TTM) and local recurrence rate. Secondary outcomes were the effects of the presence of ESE, ESE size, and the use of adjuvant external beam radiotherapy (EBRT) on the primary outcomes. RESULTS: Of 172 enucleated UMs, 32 (18.6%) had ESE. Over a median follow-up period of 33.7 months (range = 1.1-163.7 months), 91 (52.9%) patients died. The median length of all-cause survival of 54.1 months (range = 1.1-163.7 months). One-year, 5-year, and 10-year survival rates were 84.8%, 49.1%, and 30.9%, respectively. Eighty-four (49.7%) patients had metastatic disease. The median TTM of 42.2 months (range = 0.4-106.8 months). Proportions of patients who developed metastases within 1-year, 5-years and 10-years post-enucleation were 22.7%, 52.8%, and 71.8%, respectively. There was one instance of local orbital recurrence. ESE was associated with a significantly shorter length of survival (p = 0.03). There was a trend towards a shorter length of survival and TTM with ESE > 5 mm and those who received adjuvant EBRT. CONCLUSIONS: ESE was present in one-sixth of our cohort and was associated with a significantly shorter length of survival, particularly in the presence of ESE > 5 mm or high-risk characteristics warranting adjuvant EBRT. This data will aid prognostication of the patients in our service.

Liver resection for metastatic uveal melanoma: experience from a supra-regional centre and review of literature.

Management of liver metastases from uveal melanoma (LMUM) requires multimodal approach. This study describes evolution of liver resection for LMUM, reviewing current literature and institutional outcomes. Records of patients referred to the Melanoma Multi-Disciplinary Team between February 2005 and August 2018 were reviewed. All publications describing surgery for LMUM were identified from PubMed, Embase, and Google Scholar. Thirty-one of 147 patients with LMUM underwent laparoscopic liver biopsy, and 29 (14 females) had liver resections. Nineteen liver resections were performed locally [7 major (≥3 seg), 14 laparoscopic] without major complications or mortality. Overall survival positively correlated with the time from uveal melanoma to LMUM (Spearman's rho rs = 0.859, P < 0.0001). Overall and recurrence-free survivals were comparable following R1 or R0 resections (OS 25 vs. 28 months, P = 0.404; RFS 13 vs. 6 months, P = 0.596). R1 resection cohort had longer lead-time (median 100 vs. 24 months, P = 0.0408). Eleven publications describing liver resection for LMUM were identified and included in the narrative review. Surgery for LMUM is safe and complements multidisciplinary management. Despite heterogeneity in literature, time from diagnosis of uveal melanoma to LMUM remains a key factor affecting survival after liver resection.

Outcomes of fractionated CyberKnife radiosurgery in patients with choroidal malignant melanoma.

OBJECTIVE: The aim of this study was to evaluate local tumor control and complication development rates of fractionated CyberKnife radiosurgery (CRS) in patients with choroidal melanoma. METHODS: A total of 29 patients with choroidal melanoma were treated with fractionated CRS at Ankara Oncology Research and Training Hospital, Department of Radiotherapy between May 2009 and December 2013. Patients were treated with CRS if the initial height of the choroidal melanoma was ≥ 6 mm, or juxtapapillary and/or juxtamacular tumors with a height of >2.5 mm. Ophthalmic examinations were performed at baseline and at months 3, 6, 9 and 15 after radiotherapy. Assessment of visual acuity and measurement of tumor base dimension and height using A-scan and B-scan echography were done at each visit. RESULTS: The mean age was 56 (27-75) years. Tumor was located on choroid in 23 and on ciliochoroid in 6 patients. 86.2% of all melanomas were classified as medium sized and 23.8% as large sized. A median total dose of 5000 cGy was applied. Median tumor height decreased from 7.5 mm at baseline to 4.4 mm at the last follow-up visit (p < 0.001). Median visual acuity decreased from 0.4 at baseline to hand motion (p < 0.001). One patient had been lost to the metastatic disease and one patient had been treated with enucleation due to recurrent tumor growth. CONCLUSION: CRS is an effective and reliable local treatment modality in uveal melanoma.

Tumor Growth Rate as a Predictive Marker for Recurrence and Survival After Liver Resection in Patients with Liver Metastases of Uveal Melanoma.

BACKGROUND: Surgical management of liver metastases of uveal melanoma (LMUM) is associated with the best survival rates, especially for patients with a low tumor burden in the liver. The aim was to determine whether the tumor growth rate (TGR0) before liver resection helps predict survival in patients with resectable LMUM. METHODS: This retrospective study included 99 patients with LMUM treated with liver resection between November 2007 and November 2020. TGR0 was expressed as the percentage change in tumor volume over 1 month according to two pretreatment imaging scans. Multivariate Cox analyses identified independent predictors of disease-free survival (DFS) and overall survival (OS). RESULTS: DFS and OS had a statistically significant positive linear relationship (Spearman correlation r = 0.68, p < 0.001). A disease-free interval (DFI) > 24 months and a TGR0 ≤ 50%/month were independent factors associated with better DFS and OS. The 2-component model including TGR0 and DFI had a mean time-dependent area under the curve (AUC) of 0.81 (95% CI, 0.75-0.86) and 0.77 (95% CI, 0.67-0.87), respectively, for predicting DFS and OS. DFI with TGR0 defined three kinetic risk groups that had distinct DFS and OS outcomes (p < 0.001). Cytogenetic alterations at baseline were partially predictive factors of the kinetic risk score based on TGR0 and DFI. DISCUSSION: The assessment of TGR0 improves prognostic stratification by identifying patients at high risk of recurrence and poor survival after liver resection. TGR0 and DFI, reflecting tumor aggressivity, have the potential to be important markers for systemic adjuvant decisions.

Retrospective analysis of secondary enucleation for uveal melanoma after plaque radiotherapy.

BACKGROUND: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Plaque brachytherapy (PRT) is widely accepted as an effective globe-conserving treatment modality for UM. However, local treatment failure and complications lead to the enucleation of irradiated eyes. We conducted this study to explore the causes and long-term prognosis for UM patients who accepted secondary enucleation after plaque radiotherapy. METHODS: This was a retrospective cohort study. Data of patients who underwent secondary enucleation for UM after plaque radiotherapy, from July 2007 to July 2019, at Beijing Tongren Hospital were analyzed. Kaplan-Meier analysis was performed to assess the probability of indications, metastasis, and metastasis-related death. Cox regression analysis was used to analyze associations of the prognostic factors. RESULTS: Eight hundred and eighty patients were clinically diagnosed with uveal melanoma and initially treated by iodine-125 plaque radiotherapy, 132 of whom underwent secondary enucleation and pathological examination in the same hospital. Fifty-two (39.4%) eyes were enucleated simply because of uncontrollable neovascular glaucoma (NVG). Forty-four (33.3%) patients suffered from tumor recurrence. Tumor non-response occurred in 18 (13.6%) cases. Ten (7.6%) eyes received enucleation entirely due to other types of glaucoma. Failure to preserve the eyes for other reasons occurred in eight (6.1%) patients. At a median follow-up of 58.1 [IQR: 40.9-90.5] months, the systemic spread was detected in 45 (34.1%) patients, and 38 of them died. On multivariate analysis, tumor largest basal diameter (HR 1.15 [95% CI: 1.01, 1.31]), tumor non-response (HR 7.22 [95% CI: 2.63, 19.82]), and recurrence (HR 3.29 [95% CI: 1.54, 7.07]) were risk factors for metastasis. Increased age (HR 1.54 [95% CI: 1.07, 2.23]), tumor non-response (HR 7.91 [95% CI: 2.79, 22.48]), and recurrence (HR 3.08 [95% CI: 1.13, 7.23]) were risk factors for metastasis-related death. CONCLUSIONS: NVG was the major reason for secondary enucleation for Chinese UM patients after PRT. Tumor non-response and recurrence were associated with a significantly higher risk of long-term metastasis and metastasis-related death.

A case of ciliary body cyst with extrascleral extension.

We report the case of a 3-year-old girl who presented with an elevated, darkly colored, subconjunctival lesion found to be a ciliary body cyst with extrascleral extension. The patient was treated with excision of bulbar conjunctiva, sclera, and the ciliary body cystic lesion. The defect was repaired with a scleral patch graft. The patient had a small recurrent cyst after 15 months of postsurgical follow-up, and the procedure was repeated. There was no recurrence at follow-up 1 year after the second surgery.

Surgical Approach in Intraocular Tumors

Surgery in intraocular tumors is done for excision/biopsy and the management of complications secondary to the treatment of these tumors. Excision/biopsy of intraocular tumors can be done via fine-needle aspiration biopsy (FNAB), transretinal biopsy (TRB), partial lamellar sclerouvectomy (PLSU), and endoresection. FNAB, TRB, and PLSU can be used in tumors that cannot be diagnosed by clinical examination and other ancillary testing methods. PLSU is employed in tumors involving the iridociliary region and choroid anterior to the equator. Excisional PLSU is performed for iridociliary and ciliary body tumors with less than 3 clock hours of iris and ciliary body involvement and choroidal tumors with a base diameter less than 15 mm. However, for biopsy, PLSU can be employed with any size tumor. Endoresection is a procedure whereby the intraocular tumor is excised using vitrectomy techniques. The rationale for performing endoresection is based on the fact that irradiated uveal melanomas may cause complications such as exudation, neovascular glaucoma, and intraocular pigment and tumor dissemination (toxic tumor syndrome), and removing the dead tumor tissue may contribute to better visual outcome. Endoresection is recommended 1-2 weeks after external radiotherapy. Pars plana vitrectomy is also used in the management of complications including vitreous hemorrhage, retinal detachment, and epiretinal membrane that can occur after treatment of posterior segment tumors using radiotherapy and transpupillary thermotherapy. It is important to make sure the intraocular tumor has been eradicated before embarking on such treatment.

Vasculogenic mimicry correlates to presenting symptoms and mortality in uveal melanoma.

PURPOSE: Fluid-conducting extracellular matrix patterns known as vasculogenic mimicry (VM) have been associated with poor prognosis in uveal melanoma and other cancers. We investigate the correlations between VM, presenting symptoms, mortality, and the area density of periodic acid-Schiff positive histological patterns (PAS density). METHODS: Sixty-nine patients that underwent enucleation for uveal melanoma between 2000 and 2007 were included. Clinicopathological parameters presenting symptoms and outcomes were collected. Histological tumor sections were evaluated for VM and PAS density was quantified with digital image analysis. RESULTS: Thirty-four patients (49%) presented with blurred vision. 18 (26%) with a shadow in the visual field, 7 (10%) with photopsia and/or floaters, and 2 (3%) with metamorphopsia. Nine patients (13%) had no symptoms at all. Median follow-up was 16.7 years (SD 2.6). A shadow in the visual field, but no other symptom, was positively correlated with the presence of VM (φ 0.70, p < 0.001) and greater PAS density (p < 0.001). In multivariate regression, retinal detachment (RD), presence of VM, and PAS density ≥ median were independent predictors of a shadow, but not tumor distance to the macula, tumor apical thickness, tumor diameter, or ciliary body engagement. The presence of VM was associated with significantly shorter cumulative disease-specific survival (Wilcoxon p = 0.04), but not PAS density ≥ median, presenting symptoms or RD (p > 0.28). CONCLUSION: Tumors from uveal melanoma patients that report a visual field shadow are likely to display VM and greater PAS density, likely explaining the previously reported association between this symptom and poor prognosis.